Dai Chunyang, Zhang Chengfang, Sun Xiaoxi, Pan Qing, Peng Jing, Shen Jilong, Ma Xiaoling
Department of Laboratory Medicine, Anhui Provincial Hospital, Anhui Medical University, Hefei, China.
Department of Laboratory Medicine, Bengbu Medical College, Bengbu, China.
Int J Biochem Cell Biol. 2016 Jul;76:107-14. doi: 10.1016/j.biocel.2016.04.005. Epub 2016 Apr 19.
LukS-PV, a component of Panton-Valentine leukocidin, is a pore-forming cytotoxin secreted by Staphylococcus aureus. Here we examined the potential effect of LukS-PV in differentiation of human leukemia cells and the underlying mechanism. We found that LukS-PV could induce differentiation of human acute myeloid leukemia (AML) cells, including AML cell lines and primary AML blasts, as determined by morphological changes, phagocytosis assay and expression of CD14 and CD11b surface antigens. In addition, LukS-PV activated the extracellular signal-regulated kinase (ERK) pathway and significantly upregulated the phosphorylation of c-JUN and c-FOS transcriptional factors in the process of differentiation. Inhibiting ERK pathway activation with U0126 (a MEK1/2 inhibitor) markedly blocked LukS-PV-induced differentiation and decreased the phosphorylation of c-JUN and c-FOS. These findings demonstrate an essential role for the ERK pathway together with c-JUN and c-FOS in the differentiation activity of LukS-PV. Taken together, our data suggest that LukS-PV could be a potential candidate as a differentiation-inducing agent for the therapeutic treatment of AML.
LukS-PV是杀白细胞素的一个组分，是由金黄色葡萄球菌分泌的一种成孔细胞毒素。在此，我们研究了LukS-PV对人白血病细胞分化的潜在影响及其潜在机制。我们发现，LukS-PV可诱导人急性髓系白血病（AML）细胞分化，包括AML细胞系和原发性AML原始细胞，这可通过形态学变化、吞噬试验以及CD14和CD11b表面抗原的表达来确定。此外，LukS-PV激活了细胞外信号调节激酶（ERK）通路，并在分化过程中显著上调了c-JUN和c-FOS转录因子的磷酸化水平。用U0126（一种MEK1/2抑制剂）抑制ERK通路激活可显著阻断LukS-PV诱导的分化，并降低c-JUN和c-FOS的磷酸化水平。这些发现证明了ERK通路以及c-JUN和c-FOS在LukS-PV的分化活性中起着至关重要的作用。综上所述，我们的数据表明LukS-PV可能是一种用于AML治疗的潜在分化诱导剂候选物。
